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Cerebrospinal Fluid Tau and -Amyloid 42 Proteins Identify Alzheimer Disease in Subjects With Mild Cognitive Impairment

M. Riemenschneider, MD; N. Lautenschlager, MD; S. Wagenpfeil, PhD; J. Diehl, MD; A. Drzezga, MD; A. Kurz, MD

Arch Neurol. 2002;59:1729-1734.

Context  Cerebrospinal fluid tau protein and -amyloid 42 (A42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI).

Objective  To investigate the potential of cerebrospinal fluid tau and A42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months.

Design  An 18-month prospective study.

Setting  Clinical follow-up study of community-residing subjects with MCI.

Main Outcome Measures  Cerebrospinal fluid tau and A42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis.

Results  Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P = .002) and subjects with progressive MCI (P = .003) compared with subjects who had stable MCI. Cerebrospinal fluid A42 levels were significantly lower in patients who progressed to probable AD (P = .007) and those with progressive MCI (P = .04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P = .02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P = .03).

Conclusion  Our results indicate that altered tau and A42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.

From the Neurochemical and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy (Dr Riemenschneider), Institute of Medical Statistics and Epidemiology (Dr Wagenpfeil), Department of Psychiatry (Drs Diehl and Kurz), and Department of Nuclear Medicine (Dr Drzezga), Technische Universität München, Munich, Germany; and the Department of Psychiatry and Behavioural Science, University of Western Australia, Perth (Dr Lautenschlager).

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